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2011| July-August | Volume 43 | Issue 4
Online since
July 22, 2011
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RESEARCH ARTICLES
Evaluation of the anti-inflammatory activity of
Aegle marmelos
(Bilwa) root
Jyoti M Benni, MK Jayanthi, RN Suresha
July-August 2011, 43(4):393-397
DOI
:10.4103/0253-7613.83108
PMID
:21844992
Aims and objectives:
The purpose of this study was to evaluate and compare the anti-inflammatory activity of the aqueous root bark extract of
Aegle marmelos
(Bilwa) in experimental acute and chronic inflammatory animal models.
Materials and Methods:
Aqueous extract of root bark of Bilwa was prepared and tested for anti-inflammatory activity in albino rats weighing 150-280 grams. The animals were randomly divided into 3 groups of 6 each; one group served as control and other two groups received indomethacin and Bilwa orally 1 hour prior to experimentation. The
in vivo
anti-inflammatory activity was studied using the acute (Carrageenan induced paw edema) and chronic (Cotton pellet induced granuloma) animal models. Anti-inflammatory activity was expressed as Percent inhibition (PI). Statistical analysis was performed using One-way analysis of variance (ANOVA) followed by Scheffe's post hoc test. P < 0.05 was considered statistically significant.
Results:
The PI with indomethacin and Bilwa in carrageenan induced paw edema were 52.7% and 46% and in cotton pellet induced granuloma were 24.7% and 9.2% respectively. Indomethacin showed highly significant anti-inflammatory activity in both the models. However, Bilwa showed highly significant activity in acute model and but a trend of anti-inflammatory activity in chronic model studied.
Conclusions:
As Bilwa showed significant anti-inflammatory activity in the models studied, it can be a promising anti-inflammatory agent.
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SHORT COMMUNICATIONS
Antidiabetic activity of ethanolic extract of tubers of
Dioscorea alata
in alloxan induced diabetic rats
V Maithili, SP Dhanabal, S Mahendran, R Vadivelan
July-August 2011, 43(4):455-459
DOI
:10.4103/0253-7613.83121
PMID
:21845005
Objective:
To evaluate the antidiabetic activity of ethanolic extract of
Dioscorea alata
in glucose loaded and alloxan induced diabetic rats.
Materials and Methods:
The authenticated tubers of
D. alata (DA)
(JSSCPDP/2008/157) were collected from Dharmapuri, Tamil Nadu. The ethanol extract was tested for hypoglycemic activity in normal rats. In oral glucose tolerance test, glucose (3 g/kg, p.o.) was administered to non diabetic control, metformin (250 mg/kg, p.o.) and
DA
extract (100 and 200 mg/kg, p.o.) to treat treated rats. Diabetes mellitus was induced by alloxan monohydrate (120 mg/kg, i.p.) in physiological saline after overnight fasting for 18 hours.
DA
extract (100 and 200 mg/kg, p.o.) and standard drug metformin (250 mg/kg, p.o.) were administered to diabetic rats for 21 days. Fasting blood glucose level and changes in body weight were measured on days 0, 7, 14, and 21. At the end of 21
st
day, serum lipid profile, total protein, albumin, and creatinine were assessed.
Results:
In glucose loaded normal rats, the treatment with the extract of
DA
had shown a highly significant reduction (
P
< 0.001) in blood glucose levels at the doses of 100 and 200 mg/kg, respectively. The extract did not produce hypoglycemic activity at both the dose levels in normal, fasted rats. In alloxan induced diabetic rats, the body weight of the
DA
extract treated animals had shown a significant increase (
P
< 0.001) after 21 days treatment. The blood glucose level was reduced significantly by 47.48% and 52.09% after 21 days treatment at dose levels 100 and 200 mg/kg, respectively. Serum lipid levels, total protein, albumin, and creatinine were reversed toward near normal in treated rats as compared to diabetic control.
Conclusion:
The results indicate that ethanol extract of
DA
tubers possesses significant antidiabetic activity.
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RESEARCH ARTICLES
Managing diabetic ketoacidosis in non-intensive care unit setting: Role of insulin analogs
R Karoli, J Fatima, T Salman, S Sandhu, R Shankar
July-August 2011, 43(4):398-401
DOI
:10.4103/0253-7613.83109
PMID
:21844993
Aim:
To compare the efficacy and safety of rapid acting insulin analog lispro given subcutaneously with that of standard low-dose intravenous regular insulin infusion protocolin patients with mild to moderate diabetic ketoacidosis.
Materials and Methods:
In this prospective, randomized and open trial, 50 consecutive patients of mild to moderate diabetic ketoacidosis were randomly assigned to two groups. The patients in group 1 were treated with intravenous regular insulin infusion and admitted in intensive care unit. The patients in group 2 were treated with subcutaneous insulin lispro 2 hourly and managed in the emergency medical ward. Response to therapy was assessed by duration of treatment and amount of insulin administered until resolution of hyperglycemia and ketoacidosis, total length of hospital stay, and number of hypoglycemic events in the two study groups.
Results:
The baseline clinical and biochemical parameters were similar between the two groups. There were no differences in the mean duration of treatment and amount of insulin required for correction of hyperglycemia and ketoacidosis. There was no mortality and no difference in the length of hospital stay between the two groups. The length of stay and amount of insulin required for correction of hyperglycemia was greater in patients who had infection as the precipitating cause than those with poor compliance. The hypoglycemic events were higher in the regular insulin group (2 vs1) than in the lispro group.
Conclusion:
Patients with uncomplicated diabetic ketoacidosis can be managed in the medical wards with appropriate supervision and careful monitoring. Rapid acting insulin analog lispro is a safe and effective alternative to intravenous regular insulin for this subset of patients.
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SHORT COMMUNICATIONS
Antihyperglycemic and hypolipidemic activity of methanolic extract of
Amaranthus viridis
leaves in experimental diabetes
Krishnamurthy Girija, Kuruba Lakshman, Nagaraj Pruthvi, Pulla Udaya Chandrika
July-August 2011, 43(4):450-454
DOI
:10.4103/0253-7613.83120
PMID
:21845004
To investigate the antihyperglycemic and hypolipidemic effects of methanolic extract of leaves of
Amaranthus viridis
(MEAV) in normal and Streptozotocin (STZ) induced diabetic rats. The anti-hyperglycemic and hypolipidemic activity of methanolic extract of leaves of
Amaranthus viridis
was evaluated by using normal and STZ induced diabetic rats at dose of 200 mg/kg and 400 mg/kg by mouth per day for 21 days. Blood glucose levels and body weight was monitored at specific intervals, and different biochemical parameters, serum cholesterol, serum triglyceride, high density lipoprotein, low density lipoprotein, very low density lipoprotein were also assessed in the experimental animals. Histology of pancreas was performed. The statistical data indicated a significant increase in the body weight, decrease in the blood glucose, total cholesterol and serum triglycerides after treatment with MEAV. High density lipoprotein (HDL) cholesterol level was significantly increased when treated with extract. Histologically, focal necrosis was observed in the diabetic rat pancreas; however, was less obvious in treated groups. The MEAV has beneficial effects in reducing the elevated blood glucose level and body weight changes, and improves the lipid profile of STZ induced rats.
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RESEARCH ARTICLES
Protective effects of
Phyllanthus amarus
aqueous extract against renal oxidative stress in Streptozotocin -induced diabetic rats
R Karuna, Vijaya G Bharathi, Sreenivasa S Reddy, B Ramesh, D Saralakumari
July-August 2011, 43(4):414-418
DOI
:10.4103/0253-7613.83112
PMID
:21844996
Aim and Objectives:
In the present study, we have evaluated the antihyperglycemic, hypolipidemic and antioxidant activities of aqueous extract of
Phyllanthus amarus
(PAAEt) in streptozotocin (STZ)-induced diabetic rats.
Materials and Methods:
PAAEt was administered at 200 mg/kg body weight/day to normal treated (NT-group) and STZ-induced diabetic treated rats (DT-group) by gavage for eight weeks. During the experimental period, blood was collected from fasted rats at 10 days intervals and plasma glucose level was estimated. The plasma lipid profile was estimated at the end of experimental period. After the treatment, period kidney lipid peroxidation (LPO), protein oxidation and reduced glutathione (GSH) were estimated and antioxidant enzymes viz., glutathione reductase (GR), glutathione peroxidase (GPx) and glutathione-S-transferase (GST), catalase (CAT) and superoxide dismutase (SOD) were also assayed.
Results:
The significant decrease in the body weight, hyperglycemia and hyperlipidemia observed in STZ-induced diabetic rats (D-group) were rectified with PAAEt treatment in diabetic treated group (DT-group). D-group rats showed increased renal oxidative stress with increased LPO and protein oxidation. DT-group showed a significant decrease in renal LPO, protein oxidation and a significant increase in GSH content and GR, GPx and GST activities when compared with D-group. The activities of SOD and CAT decreased significantly in D-group, but were normalized in DT-group. Normal rats treated with PAAEt (NT-rats) showed a significant decrease in lipid profile, renal LPO and protein oxidation, with significant increase in renal GSH and activities of antioxidant enzymes compared to normal rats (N-group).
Conclusion:
Our results demonstrated that PAAEt with its antidiabetic, hypolipidemic and antioxidant properties could be a potential herbal medicine in treating diabetes and renal problems.
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Nanotechnology in oncology: Characterization and
in vitro
release kinetics of cisplatin-loaded albumin nanoparticles: Implications in anticancer drug delivery
Saikat Das, Lavanya Jagan, Rajesh Isiah, B Rajesh, Selvamani Backianathan, J Subhashini
July-August 2011, 43(4):409-413
DOI
:10.4103/0253-7613.83111
PMID
:21844995
Context:
Nanotechnology is an empowering technology that holds promise in cancer therapeutics by increasing the ratio of tumor control probability to normal tissue complication probability. It can increase the bioavailability of the drug at the target site, reduce the frequency of administration and reach otherwise lesser-accessible sites. The present study shows the feasibility of the cisplatin-loaded albumin nanoparticle as a sustained delivery system.
Aims:
Cisplatin is one of the most widely used chemotherapeutic agents for the treatment of malignant disorders. Conventional cisplatin formulation given as intravenous infusion has low bioavailability to the target organ in addition to significant side-effects, like ototoxicity and nephrotoxicity. The aim of this study was to develop a protein-based nanoparticulate system for sustained release of cisplatin.
Materials and Methods:
Nanoparticles were prepared by the coacervaton method of microcapsulation and chemical cross-linking with glutaraldehyde. Particle size was characterized by dynamic light scattering and transmission electron microscopy.
Results and Conclusions:
Using the coacervation method, nanoparticles of less than 70 nm diameter were produced. Drug encapsulation measured by ultraviolet spectroscopy varied from 30% to 80% for different ratios of cisplatin and protein.
In vitro
release kinetics shows that the nanoparticle-based formulation has biphasic release kinetics and is capable of sustained release compared with the free drug (80% release in 45 h). The study proves the feasibility of the albumin-based cisplatin nanoparticle formulation as a sustained release vehicle of cisplatin.
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SHORT COMMUNICATIONS
Effect of Unex on ethylene glycol-induced urolithiasis in rats
Elias Edwin Jarald, Pankaj Kushwah, Sheeja Edwin, Suhail Asghar, Showkat Ahmad Patni
July-August 2011, 43(4):466-468
DOI
:10.4103/0253-7613.83124
PMID
:21845008
This study was aimed to evaluate the effectiveness of the Unex capsule on albino rats as a preventive agent against the development of kidney stones. The Unex capsule is a marketed product of Unijules Life Sciences, Nagpur, containing the extracts of Boerhaavia diffusa and Tribulus terrestris. Activity of Unex was studied using the ethylene glycol-induced urolithiasis model. Standard drug used was Cystone. Several parameters were used including urinary volume, urine pH, urine analysis, and serum analysis to assess the activity. The results indicated that the administration of Unex to rats with ethylene glycol-induced lithiasis significantly reduced and prevented the growth of urinary stones (P < 0.01). Also, the treatment of lithiasis-induced rats by Unex restored all the elevated biochemical parameters (creatinine, uric acid, and blood urea nitrogen), restored the urine pH to normal, and increased the urine volume significantly (P < 0.01) when compared to the model control drug. This study supports the usage of Unex in urolithiasis and the utility could further be confirmed in other animal models.
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EDUCATIONAL FORUM
Non-inferiority clinical trials: Practical issues and current regulatory perspective
Sandeep K Gupta
July-August 2011, 43(4):371-374
DOI
:10.4103/0253-7613.83103
PMID
:21844987
Non-inferiority clinical trials are being performed with an increasing frequency now-a-days, because it helps in finding a new treatment that have approximately the same efficacy, but may offer other benefits such as better safety profile. Non-inferiority clinical trials aim to demonstrate that the test product is no worse than the comparator by more than a pre-specified small amount. There are several fundamental differences between non-inferiority and superiority trials. Some practical issues concerning the non-inferiority trials are assay sensitivity, choice of the non-inferiority margin, sample size estimation, choice of active-control, and analysis of non-inferiority clinical trials. For serious infections such as hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia, community-acquired bacterial pneumonia, and acute bacterial skin and skin structure infections, the United States Food and Drug Administration (US FDA) has recently recommended that it is possible to define a reliable and consistent estimate of the efficacy of active treatment relative to placebo from available data, which can serve as the basis for defining a new inferiority margin for an active-controlled, non-inferiority trial. But for some indications with a high rate of resolution without antibacterial drug therapy such as acute bacterial sinusitis (ABS), acute bacterial exacerbation of chronic bronchitis (ABECB), and acute bacterial otitis media (ABOM), the US FDA has recommended that the available data will not support the use of a non-inferiority design and other trial designs (i.e., superiority designs) should be used to provide the evidence of effectiveness in these three indications.
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RESEARCH ARTICLES
Comparison of nebivolol and atenolol on blood pressure, blood sugar, and lipid profile in patients of essential hypertension
VA Badar, Sachin K Hiware, Meena P Shrivastava, VR Thawani, MM Hardas
July-August 2011, 43(4):437-440
DOI
:10.4103/0253-7613.83117
PMID
:21845001
Background:
Nebivolol is a third-generation β-blocker, with highest β
1
selectivity and nitric-oxide-derived vasodilatation. It also exhibits antiproliferative and antioxidant property that has beneficial metabolic profile compared to second-generation β blockers like atenolol. This study was planned to study the comparative effects of nebivolol and atenolol on metabolic parameters in patients with essential hypertension.
Materials and Methods:
A prospective, randomized, parallel, open-label clinical study was carried out on patients with essential hypertension. The patients were randomly assigned to receive tablet atenolol (Group A) and nebivolol (Group B) for a period of 24 weeks. Investigations were carried out at baseline and at the end of study period, that is, 24 weeks. Out of 69 patients, 60 completed the study and the data was analyzed using student's t-test. P < 0.05 was considered statistically significant.
Results:
Atenolol and nebivolol both showed significant (P < 0.001) antihypertensive action after 24 weeks. Mean blood sugar and lipid profile were found to be significantly (P < 0.001) elevated after 24 weeks of treatment with atenolol but not with nebivolol. Heart rate was significantly (P < 0.001) decreased in both groups at 24 weeks.
Conclusion:
In view of metabolic adverse effects of atenolol, nebivolol is the better choice whenever β-blockers have to be used in essential hypertension.
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The protective effect of
Rubia cordifolia
against lead nitrate-induced immune response impairment and kidney oxidative damage
Shweta lodi, Veena Sharma, Leena Kansal
July-August 2011, 43(4):441-444
DOI
:10.4103/0253-7613.83118
PMID
:21845002
Objectives:
To evaluate the in vivo antioxidant activity of the ethanolic extract of the roots of
Rubia cordifolia
(RC) and to study its influence on lead nitrate-induced impairment of immune responses.
Materials and Methods:
Seventy-two adult male Swiss albino mice were used for biochemical and immunological studies and were divided into six groups of six mice each. Mice were treated with lead nitrate (40 mg/kg, orally) either alone and or in combination with RC (50 and 100 mg/kg body weight) daily for 40 days. For immunological studies, all mice were challenged twice with sheep RBC with on days 14 and 20 of the experiment. The immune function was assessed using macrophage yield, viability of macrophage, phagocytic index, serum immunoglobulin level, and plaque forming cell count (PFC), whereas the oxidative stress was assessed by estimating lipid peroxidation (LPO), reduced glutathione (GSH) content, and the activities of superoxide dismutase (SOD) and catalase (CAT).
Results:
Lead nitrate administration induced a significant (P<0.001) increase in LPO, whereas a significant (P<0.001) depletion of CAT and GSH in renal tissues. In addition, it also showed a significant (P<0.001) reduction in macrophage yield, viability of macrophage, phagocyte index, serum immunoglobulin level, and PFC in kidney. However, combination treatment with RC observed a significant (P<0.001) reversal of lead nitrate-induced toxicity on oxidative stress and immunological parameters.
Conclusion:
The lead nitrate-induced immunosuppression is due to oxidative stress and RC can prevent the same by virtue of its in vivo antioxidant property.
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Effect of Montelukast on bradykinin-induced contraction of isolated tracheal smooth muscle of guinea pig
A Noor, MH Najmi, S Bukhtiar
July-August 2011, 43(4):445-449
DOI
:10.4103/0253-7613.83119
PMID
:21845003
Aim:
To explore the effect of montelukast on bradykinin-induced tracheal smooth muscle contraction of isolated guinea pig trachea.
Study Design:
To study the effect of bradykinin in the absence and in the presence of montelukast on the isolated tracheal smooth muscle of a guinea pig pretreated with indomethacin (10
-6
M), phentolamine (10
-5
M), and propranalol (10
-6
M), to eliminate the effect of endogenous prostaglandins and catecholamines. The trachealis smooth muscle activity was recorded through the Isometric Force Displacement Transducer on a Four Channel Oscillograph. A cumulative dose-response relationship was demonstrated by adding successive doses of bradykinin on the tracheal strips, starting with 11 μg to 77 μg of 10
-4
concentration. A similar procedure was repeated in the presence of montelukast 0.5 μg/ml, which, was equal to approximate C
max
achieved in vivo with a 10 mg oral dose of montelukast, and in the presence of 1 μg/ml of montelukast.
Statistical Analysis:
Data was expressed as mean ± standard error (SEM), and was analyzed using the SPSS version 15. A P value of less than 0.05 was considered significant.
Results:
Bradykinin produced a dose-dependent, reversible contraction of isolated tracheal smooth muscle. Montelukast significantly reduced the bradykinin-induced tracheal smooth muscle reactivity and shifted the bradykinin curve to the right and downwards, in the presence of both concentrations of montelukast. The mean magnitude of response achieved with 77 μg of bradykinin in the absence of montelukast was 39 mm ± 6.26, in the presence of 0.5 μg/ml of montelukast it was 24.17 mm ± 4.11, and in the presence of 1 μg/ml of montelukast it was 13 mm ± 2.6.
Conclusion:
It is concluded that montelukast significantly inhibits, in a dose-dependent manner, the bradykinin-induced contraction of the guinea pig tracheal smooth muscle, and alludes to an interaction between the bradykinin and leukotriene mediators.
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A biochemical study on the gastroprotective effect of hydroalcoholic extract of
Andrographis paniculata
in rats
Saranya Panneerselvam, Geetha Arumugam
July-August 2011, 43(4):402-408
DOI
:10.4103/0253-7613.83110
PMID
:21844994
Aim:
The aim of the present study is to evaluate the gastroprotective effect of hydroalcoholic extract of
Andrographis paniculata
(HAEAP) in male albino wistar rats.
Materials and Methods:
Rats were pretreated with HAEAP (100,200,500mg/kg b. wt for 30 days) and then gastric ulcers were induced by ethanol, aspirin, pylorus ligation and cold restraint stress models. Ulcer score was determined in all the ulcer models. pH, gastric volume, titrable acidity, pepsin, mucin, myeloperoxidase, H
+
K
+
ATPase, thiobarbituric acid reacting substances (TBARS) and antioxidant enzyme activities were assayed in ethanol-administered rats.
Results:
The ulcer score was found to be low in HAEAP-pretreated rats. Among the doses studied, 200 mg/kg b.wt was found to be optimum for significant ulcer reduction. The test drug significantly reduced the acidity, pepsin concentration, myeloperoxidase and H
+
K
+
ATPase activities in ethanol-administered rats. The elevated TBARS and decreased glutathione (GSH) and mucin levels observed during ulcerogenesis were found to be altered in HAEAP-received animals.
Conclusions:
The ulcer preventing effect of HAEAP may partly be due to its regulating effect on H
+
K
+
ATPase activity and /or mucin preserving effects. The flavonoids present in the HAEAP might be responsible for the gastroprotective action probably by maintaining the antioxidants and thiol status in the gastrointestinal tract.
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369
Comparison of the effect of vanadium and deferoxamine on acetaminophen toxicity in rats
H Najafzadeh, A Rezaie, AM Masoodi, S Mehrzadi
July-August 2011, 43(4):429-432
DOI
:10.4103/0253-7613.83115
PMID
:21844999
Aim:
Acetaminophen (APAP) can change to toxic metabolites at high dose; if these metabolites are in high amounts, the body will be unable to neutralize them, and several tissues including liver will be damaged. In the present study, the effect of vanadium was compared with deferoxamine on hepatotoxicity and also kidney function during APAP administration in rats.
Material and Methods:
The study was done in 5 groups (5 rats in each group): group I to V, respectively, received normal saline, APAP, APAP + deferoxamine, APAP + vanadium, and vanadium. At the end of the study, blood was collected and serum was separated for laboratory tests. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), blood urea nitrogen (BUN), creatinine, sodium, and potassium were determined. The liver of the rats were separated for tissue processing and light microscopic examination.
Results:
APAP significantly increased; ALT level and deferoxamine and vanadium prevented its elevation. Also, deferoxamine and vanadium prevented increase of AST by APAP. The change of factors, which are related to the kidney function, i.e., BUN, creatinine, sodium, and potassium were not considerable.
Conclusion:
Thus, it was observed that vanadium had better effect than deferoxamine in the prevention of hepatotoxicity induced by APAP.
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3,914
169
Fertility, developmental toxicity and teratogenicity in albino rats treated with methanol sub-fraction of
Carica papaya
seeds
S Shrivastava, AS Ansari, NK Lohiya
July-August 2011, 43(4):419-423
DOI
:10.4103/0253-7613.83113
PMID
:21844997
Objective:
To evaluate the status of fertility, developmental stages during gestation and teratological changes, if any, following oral administration of methanol sub-fraction (MSF) of the benzene chromatographic fraction of the chloroform extract of the seeds of
Carica papaya
in rats.
Materials and Methods:
The MSF was administered at the doses of 50 mg contraceptive dose (CD), 100 mg (2x CD), 250 mg (5x CD) and 500 mg (10x CD)/kg body wt/day along with vehicle-treated control using 10 male and 20 female Wistar rats in each group. Necropsies were performed one day before the expected parturition. Status of gravid/non-gravid uterus, the number of corpora lutea in the ovary, implantation status, fetal wellbeing, fetal resorption, fetal body weight, external, visceral and skeletal malformations were recorded.
Results:
Pregnancies were recorded in vehicle-treated control animals and in the animals treated with 50 mg/kg body wt/day. The animals treated with 2x CD, 5x CD and 10x CD did not get pregnant. The fetuses and the status of the ovary, uterus and implantation, fetal body weight, soft tissues and skeletal structures were recorded normal. Data were comparable to those of control.
Conclusion:
The results suggest that the test substance had no developmental toxicity and teratogenicity which could affect pregnancy, implantation and gestation.
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Influence of
Momordica charantia
on oxidative stress-induced perturbations in brain monoamines and plasma corticosterone in albino rats
Ch. Naga Kavitha, S Manohar Babu, ME Bhanoji Rao
July-August 2011, 43(4):424-428
DOI
:10.4103/0253-7613.83114
PMID
:21844998
Objectives:
The objective of this study was to evaluate the antistress activity of
Momordica charantia
(MC) fruit extract on stress-induced changes in albino rats and also to explore attenuating effects of MC on in vitro lipid peroxidation in rat brain.
Materials and Methods:
In this study, Wistar albino rats (180-200 g) were used. Plasma corticosterone and monoamines-5-hydroxy tryptamine (5-HT), norepinephrine (NE), epinephrine (E) and dopamine (DA) in cortex, hypothalamus and hippocampus regions of brain were determined in animals under different stressful conditions. Ethanolic fruit extract of MC, at doses of 200 and 400 mg/kg, was used. The oxidative stress paradigms used in in vivo models were acute stress (AS) and chronic unpredictable stress (CUS). Panax quinquefolium (PQ) was used as a standard in in vivo models and ascorbic acid was used as a reference standard in the in vitro method.
Results:
Subjecting the animals to AS (immobilization for 150 min once only) resulted in significant elevation of plasma corticosterone levels and brain monoamine levels. Pretreatment with MC at doses of 200 and 400 mg/kg p.o. significantly countered AS-induced changes and a similar effect was exhibited by PQ at 100 mg/kg p.o. In the CUS regimen (different stressors for 7 days), plasma corticosterone levels were significantly elevated whereas the levels of 5-HT, NE, E, and DA were depleted significantly. Pretreatment with MC (200 and 400 mg/kg) attenuated the CUS-induced changes in the levels of above monoamines in cortex, hypothalamus, and hippocampus regions of brain and plasma corticosterone in a dose-dependent manner. Furthermore, MC extract (1000-5000 μg/mL) exhibited a significant quenching effect on in vitro lipid peroxidation indicating its strong antioxidant activity which was compared with ascorbic acid.
Conclusions:
This study reveals the antistress activity of MC as it significantly reverted the stress-induced changes, and the activity might be attributed to its antioxidant activity since stress is known to involve several oxidative mechanisms.
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REVIEW ARTICLE
A brief review on recent developments in animal models of schizophrenia
MS Trivedi, T Jarbe
July-August 2011, 43(4):375-380
DOI
:10.4103/0253-7613.83104
PMID
:21844988
Number of patients suffering from schizophrenia is increasing daily, subsequently, increasing the need of proper medication to treat the symptoms and eventually improve the patients' condition. However, all the progress for designing or discovering medication comes to a standstill, as the symptomatic treatment can only be done in the patients, but performing clinical trials with all the possible candidate drugs in human beings and patients is unethical. Thus, the need arises for proper animal and non-human primate animal models of the disease, which would not only serve the purpose of understanding the disease in a better physiological setting, but also would allow the scientists to focus on developing a therapeutically effective and potent medication for treating this hazardous disease. This brief review article focuses on a few animal models which are generally used for carrying out studies on schizophrenic symptoms in research labs and industry worldwide. The paper also tries to validate the pre-clinically available models based on certain specified criteria like the predictive constructive and face validity. Thus, the paper gives guidance toward the mechanistic and traditional models of schizophrenia applying some of the newer principles and helps researchers in deciding a particular relevant model for their own purpose.
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DRUG WATCH
Cholestatic hepatitis with intravenous ceftriaxone
Inderpal Kaur, Jatinder Singh
July-August 2011, 43(4):474-475
DOI
:10.4103/0253-7613.83133
PMID
:21845011
Drug-induced liver injury is a major health problem. Its predominant forms include acute hepatitis, cholestasis, and a mixed pattern. Ceftriaxone is a third-generation cephalosporin and is widely used in the postoperative period due to its wider spectrum, longer half-life, and better tissue penetrability. Earlier cases of high aminotransferase levels and hepatitis have also been reported with the use of ceftriaxone. Here we report a case of cholestatic hepatitis with intravenous ceftriaxone.
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158
RESEARCH ARTICLES
Tacrolimus and 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors: An interaction study in CYP3A5 non-expressors, renal transplant recipients
Paraskevi F Katsakiori, Eirini P Papapetrou, Dimitrios S Goumenos, George C Nikiforidis, Christodoulos S Flordellis
July-August 2011, 43(4):385-388
DOI
:10.4103/0253-7613.83106
PMID
:21844990
Objectives:
Atherosclerosis is a significant factor affecting long-term outcome in renal transplant recipients. Studies have been conducted to determine the pharmacogenomic pathways involved in statin efficacy, efficiency, and adverse effect likelihood. However, little is known about the influence of statins on tacrolimus kinetics. The aim of this study was to investigate possible pharmacological interactions between tacrolimus and statins in CYP3A5 non-expressors, renal transplant recipients.
Materials and Methods:
Twenty-four patients, treated with tacrolimus (n=24), methylprednisolone (n=24), and mycophenolate mofetil (n=19)/azathioprine (n=1)/everolimus (n=4), participated in the study. After an observation time of 112±36 days, statins, namely, atorvastatin (n=12), simvastatin (n=8), pravastatin (n=2), or fluvastatin (n=2), were administered for additional 101±34 days. DNA was extracted from whole blood sample and polymerase chain reaction followed by restriction fragment length polymorphism analysis was used for CYP3A5 genotyping. Student's t-test and Mann-Whitney test were used to test the significance of difference in variables that passed or did not pass Kolmogorov's normality test, respectively.
Results:
No statistically significant difference was observed in tacrolimus daily dose, concentration, concentration/dose ratio, and volume of distribution before and during the administration of statins. Statistically significant decrease in serum cholesterol was observed after initiation of statins. Renal and hepatic function remained unchanged and no skeletal muscle abnormalities were reported.
Conclusions:
The results of this study show that tacrolimus and statins do not interact in terms of efficacy, efficiency, and adverse effect likelihood. No significant clinical interaction or effect was observed, even with the use of atorvastatin or simvastatin, which are metabolized by CYP3A4 such as tacrolimus.
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CASE REPORT
Deep vein and artery thrombosis associated with cetuximab-based chemoradiotherapy
Deepak Gupta, Pragya Shukla, Shyam Singh Bisht, M.L.B Bhatt, MC Pant, Kirti Srivastava
July-August 2011, 43(4):478-480
DOI
:10.4103/0253-7613.83135
PMID
:21845013
Molecular targeted agents have lower hematological toxicity. However, specific side-effects such as allergic rashes, skin reactions and high cost limit their use. We report a case of 35-year-old male patient with carcinoma of left tonsil treated with concurrent cetuximab and radiotherapy. After four weeks of treatment, the patient developed sudden onset of pain in the left calf region radiating to the left foot. Doppler study of the left lower limb revealed complete thrombosis of superficial femoral, popliteal and proximal tibial arteries and veins and no flow in anterior tibial artery and lower posterior tibial artery. Emergency embolectomy was done. After 48 h of observation, no improvement was noted. A repeat Doppler examination showed similar finding. Ultimately a left lower limb amputation was done. We report simultaneous arterio-venous thrombosis associated with cetuximab-based chemoradiotherapy. Oncologists should be aware of this possible complication to undertake early intervention.
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115
DRUG WATCH
Propofol-induced violent coughing in a patient with Becker's muscular dystrophy
Amit Jain
July-August 2011, 43(4):476-477
DOI
:10.4103/0253-7613.83134
PMID
:21845012
Propofol anesthesia is often associated with decreased incidence of gagging, coughing or laryngospasm, and provides intense suppression on airway reflex during tracheal intubation and laryngeal mask airway insertion. Propofol pretreatment is also effective in reducing the occurrence of opioid-induced coughing. These benefits are often attributed to bronchodilator and sedative effects of propofol. However, severe coughing following sedative doses of 1% propofol has not been reported so far. We report a rare case of violent coughing following low-dose propofol infusion in a patient with Becker's muscular dystrophy.
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EDITORIAL
The promise of phytoestrogens
Behram S Anklesaria
July-August 2011, 43(4):369-370
DOI
:10.4103/0253-7613.83102
PMID
:21844986
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3,791
514
LETTERS TO THE EDITOR
A case of look-alike medication errors
Hetal D Shah, Megha Shah
July-August 2011, 43(4):482-483
DOI
:10.4103/0253-7613.83127
PMID
:21845015
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173
RESEARCH ARTICLES
Antidiabetic and vasoprotective activity of lithium: Role of glycogen synthase kinase-3
Nilesh R Kanzariya, Rameshvar K Patel, Natvar J Patel
July-August 2011, 43(4):433-436
DOI
:10.4103/0253-7613.83116
PMID
:21845000
Objectives:
Lithium is a drug of choice in maniac disorder. Lithium inhibits the glycogen synthase kinase-3 (GSK-3), an enzyme involved in the insulin signalling pathway. Elevated levels of GSK-3 were found in diabetic rats and humans. We aimed to determine the effect of lithium chloride in diabetes and associated vascular complications in diabetic rats.
Materials and Methods:
Type 2 diabetes was induced by high fat diet and low dose of streptozotocin. Diabetic rats were divided into diabetic control and lithium chloride treatment groups. Lithium chloride was used as a GSK-3 inhibitor. The treatment was given for 4 weeks. Various biochemical parameters were measured before initiation and the end of treatment. Systolic blood pressure was measured by the non-invasive tail-cuff method, while various biochemical and tissue parameters were estimated for efficacy. Vasoreactivity was performed by taking the contractile response of H
2
O
2
(10
-6
M to 10
-3
M) and angiotensin II (10
-11
to 10
-7
M) in rat thoracic aortas of different groups. Statistical comparisons between all groups were performed by using two tailed one-way ANOVA followed by the Dunnett test. P-values <0.05 were considered statistically significant.
Results:
Treatment with lithium chloride significantly reduced the augmented systolic blood pressure, various biochemical parameters, and antioxidant parameters in diabetic-treated rats. Treatment also showed the decrease in augmented responses of H
2
O
2
and angiotensin II in rat thoracic aortas of treated rats.
Conclusions:
We can conclude that lithium chloride treatment reduces the diabetic state as well as diabetes-induced vascular dysfunction.
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SHORT COMMUNICATIONS
Delayed-onset akathisia due to amisulpride
Murad Atmaca, Sevda Korkmaz
July-August 2011, 43(4):460-462
DOI
:10.4103/0253-7613.83122
PMID
:21845006
Despite the fact that second-generation antipsychotics have a lower potential to cause extrapyramidal side-effects, including akathisia, their incidence is not negligible. Recent work suggests that tardive akathisia may have pharmacological differences from acute akathisia. In the present study, we have evaluated the nature of delayed-onset akathisia in patients on amisülpride monotherapy. Overall, we screened 56 patients on amisulpride treatment for 2 months at a stabilized amisulpride dose. However, 18 patients with diagnostic and statistical manual of mental disorders-IV (DSM-IV) presented with acute or delayed-onset akathisia, and all of them also met the entry criteria. The patients were evaluated at baseline and at the time when akathisia presented clinically, with respect to the Positive and Negative Syndrome Scale and Barnes Akathisia Scale (BAS). Using the primary categorical criterion of akathisia (≥2 points of the BAS global scale), 12 (21.4%) of the 56 patients experienced delayed-onset akathisia, and six (10.7%) showed acute akathisia. The mean time for onset of acute or delayed-onset akathisia was 5.8 ± 2.1 and 39.4 ± 11.3 days, respectively. The mean BAS scores at baseline and after the period of 2 months were 1.3 ± 0.6 and 3.9 ± 2.4, respectively (P < 0.001). Our results revealed that amisulpride could considerably lead to delayed-onset akathisia. However, studies comprising larger samples receiving different antipsychotics, and more comprehensive assessment, will help to ascertain the role of amisulpride in delayed-onset akathisia.
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A comparative study of efficacy and safety of arformoterol and salbutamol nebulization as rescue therapy in acute non-severe asthma
Sibes K Das, Indranil Biswas, Arun K Bandyopadhyay, Tapan D Bairagya, Somnath Bhattacharya
July-August 2011, 43(4):463-465
DOI
:10.4103/0253-7613.83123
PMID
:21845007
Arformoterol, a long-acting beta-2 agonist, has a rapid onset and long duration of action. Its role as rescue medication in acute asthma attack is undetermined. To compare the efficacy and tolerability of arformoterol with salbutamol nebulization, a study was conducted among 50 patients with acute non-severe asthma. Patients were randomly assigned to group 1 (n = 25) and group 2 (n = 25) who received three doses of salbutamol and arformoterol nebulization, respectively, at 20-min intervals. The peak expiratory flow rate (PEFR) was measured at the baseline and 5 min after each dose. The demographics and baseline characteristics were comparable between the two groups. The mean PEFR significantly increased in both these groups when compared with the baseline. The increases in the PEFR in two groups were similar after the third dose. The adverse effects in both these groups were minor. Arformoterol was as effective and safe as salbutamol in acute non-severe asthma.
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2
4,994
223
DRUG WATCH
High anion gap refractory metabolic acidosis as a critical presentation of endosulfan poisoning
Raj Kumar Sharma, Anupama Kaul, Anurag Gupta, Dharmendra Bhadauria, Narayan Prasad, Apoorva Jain, M Gurjar, Bhaskar P Rao
July-August 2011, 43(4):469-471
DOI
:10.4103/0253-7613.83126
PMID
:21845009
Organochloride insecticides are chlorinated cyclic hydrocarbons. One of such insecticides is endosulfan (6,7,8,9,10-10 hexachloro 1,5,5a,6,9,9a-hexahydro-6-methano-2,4,3-hexadithioxanthiep in 3-oxide) and it has been widely used in agriculture since 1960. The uncontrolled use of these compounds in developing countries has resulted in the deaths of animals and humans. Characteristic clinical signs following acute exposure are indicative of CNS disturbances or overstimulation. Mortality and morbidity rates are high and there is no specific antidote. We present an uncommon presentation of endosulfan poisoning in a 32-year-old male with high anion gap severe refractory metabolic acidosis. The patient was treated with continuous renal replacement therapy and was salvaged. Till date, there is no case report from India for endosulfan poisoning with severe metabolic acidosis and hypotension. Through this case report, we emphasize the role of continuous renal replacement therapy as a rescue therapy for endosulfan poisoning with severe refractory metabolic acidosis and hypotension, even though it is a non dialyzable poison.
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LETTERS TO THE EDITOR
Experimental evaluation of antipyretic and analgesic activities of aspartame
Kirtida R Tandel
July-August 2011, 43(4):486-486
DOI
:10.4103/0253-7613.83131
PMID
:21845019
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DRUG WATCH
Sodium artesunate-induced diuresis in a patient with malaria
Syed Ahmed Zaki, Preeti Shanbag, Vijay Lad, Prithi Shenoy
July-August 2011, 43(4):472-473
DOI
:10.4103/0253-7613.83129
PMID
:21845010
Sodium artesunate is used in the treatment of malaria. We report a case of sodium artesunate induced diuresis and natriuresis in a patient with malaria. Following artesunate administration there was polyuria accompanied by natriuresis that was reversed after discontinuation of artesunate treatment. The diuretic effect of artesunate can modify the course of renal failure in severe malaria. Prescribers should be aware of this effect of artesunate, so that it can be used judiciously and to the advantage of patients with severe malaria.
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LETTERS TO THE EDITOR
Direct to consumer advertising of prescription drugs on internet: A Boon or a Curse
Pratibha Khosla, Akash Khosla
July-August 2011, 43(4):483-484
DOI
:10.4103/0253-7613.83128
PMID
:21845016
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Vaccines for type 1 diabetes in the late stage of clinical development
Sandeep K Gupta
July-August 2011, 43(4):485-485
DOI
:10.4103/0253-7613.83130
PMID
:21845017
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Perspectives regarding intended learning outcomes in pharmacology
Vasudha Devi, Vinod Pallath, Tatiyana Mandal, Smita Khandelwal, Debasree Deb, Sunita Kodidela
July-August 2011, 43(4):481-482
DOI
:10.4103/0253-7613.83125
PMID
:21845014
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Authors' reply
Sapna Pradhan, UH Shah, A Mathur, S Sharma
July-August 2011, 43(4):486-487
PMID
:21845018
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RESEARCH ARTICLES
Effect of imatinib on the biochemical parameters of the reproductive function in male Swiss albino mice
AM Prasad, K Ramnarayan, K Nalini, KL Bairy
July-August 2011, 43(4):389-392
PMID
:21844991
Background:
Treatment of cancers with cytotoxic agents such as tyrosine kinase inhibiting drugs often, but not always, result in transient to permanent testicular dysfunction. Germ cells are important targets of many chemicals. Most of the drugs are genotoxins and induce irreversible effect on genetic makeup. These mutagenic changes are proportionally related to carcinogenesis. This is alarmingly dangerous in youth and children, since these effects last longer, affecting fertility or forming basis for carcinogenesis. There is paucity of reports on planned studies of imatinib on the testicular function. Hence, the study was planned to assess the effects of imatinib on biochemical markers of testicular functions in male Swiss albino mice.
Materials and Methods:
Male Swiss albino mice were treated with imatinib and sacrificed at the end of first, second, fourth, fifth, seventh, and tenth week after the last exposure to imatinib. The testis were removed, weighed, and processed for biochemical analysis.
Results:
The intratesticular testosterone level was significantly (P<0.001) reduced in treated groups and severe effect was observed on week 4 and 5. The intratesticular lactate dehydrogenase (LDH) level was significantly increased by imatinib in all treated groups up to week 5.
Conclusion:
Imatinib does affect testosterone and LDH level significantly, but this effect is reversible once the drug is withdrawn. This finding may help the clinicians to plan and address the fertility-related issues in young patients of reproductive age who are being treated with imatinib for gastrointestinal tumors and chronic myeloid leukemia.
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Effect of information, education and communication intervention on awareness about rational pharmacy practice in pharmacy students
Kunda Gharpure, Vijay Thawani, Smita Sontakke, Kiran Chaudhari, Mangesh Bankar, Rajendra Diwe
July-August 2011, 43(4):381-384
DOI
:10.4103/0253-7613.83105
PMID
:21844989
Background:
There is a growing indifference among the pharmacy practitioners towards their duty as information providers to the patients. The patients do not always get enough desired information about proper use of medicines from the prescribers also. This contributes to improper use of medicines by the patients.
Objectives:
To bring about awareness about rational pharmacy practice in pharmacy students for better service to the patients. Material and Methods: The final year students of Bachelor of Pharmacy (B. Pharm) from four colleges of Nagpur were enrolled for the study after informed consent. Their base knowledge was assessed through a written test which comprised of 27 objective questions related to rational pharmacy practice. This was followed by a series of seven articles on rational medicine use, published in leading local English news daily. The participants were reminded to read them on the day of publication of each article. As a backup, the articles were displayed on the notice board of respective colleges. Second intervention was a half day interactive session where series of six lectures were delivered to the participants on the right and wrong approaches in pharmacy practice. Posters about the do's and dont's of rational pharmacy practice were also displayed at the venue. The session was followed by a repeat test using the same pre-test to assess the change. Pre and post intervention data was compared using Fisher's Exact test.
Results:
It was observed that the intervention did bring about a positive change in the attitude and knowledge of the final year Pharmacy students about rational pharmacy practice.
Discussion:
The role of a pharmacist in health care provision is usually overlooked in India. Hence there is strong need for reinforcement in final year B. Pharm when most of the students go in for community service. Such interventions will be helpful in bringing about a positive change towards rational practice of pharmacy.
Conclusion:
This study showed that a properly timed and meticulously implemented intervention brings about a positive change in the attitude and knowledge of pharmacy students.
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